A Receptor Story: Insulin Resistance Pathophysiology and Physiologic Insulin Resensitization's Role as a Treatment Modality.

Physiologic insulin secretion consists of an oscillating pattern of secretion followed by distinct trough periods that stimulate ligand and receptor activation. Apart from the large postprandial bolus release of insulin, ß cells also secrete small amounts of insulin every 4-8 min independent of a meal. Insulin resistance is associated with a disruption in the normal cyclical pattern of insulin secretion. In the case of type-2 diabetes, ß-cell mass is reduced due to apoptosis and ß cells secrete insulin asynchronously. When ligand/receptors are constantly exposed to insulin, a negative feedback loop down regulates insulin receptor availability to insulin, creating a relative hyperinsulinemia. The relative excess of insulin leads to insulin resistance (IR) due to decreased receptor availability. Over time, progressive insulin resistance compromises carbohydrate metabolism, and may progress to type-2 diabetes (T2D). In this review, we discuss insulin resistance pathophysiology and the use of dynamic exogenous insulin administration in a manner consistent with more normal insulin secretion periodicity to reverse insulin resistance. Administration of insulin in such a physiologic manner appears to improve insulin sensitivity, lower HgbA1c, and, in some instances, has been associated with the reversal of end-organ damage that leads to complications of diabetes. This review outlines the rationale for how the physiologic secretion of insulin orchestrates glucose metabolism, and how mimicking this secretion profile may serve to improve glycemic control, reduce cellular inflammation, and potentially improve outcomes in patients with diabetes.

Physiologic Insulin Resensitization as a Treatment Modality for Insulin Resistance Pathophysiology.

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.

Accurate clinical diagnosis of malaria in a postflood epidemic: a field study in Mozambique.

OBJECTIVE: To determine the positive predictive value (PPV) of a clinical diagnosis vs laboratory testing for malaria in a remote field setting following a natural disaster. METHODS: During an observational study, as part of a disaster response in Mozambique, patients were clinically diagnosed and treated for malaria. The population included native tribes in remote areas and displaced persons in refugee camps representing all age groups, male and female. The diagnosis was made if patients exhibited at least 3 of the following historical features: fever, chills, headache, and nausea/vomiting (N/V). In addition they had to have either a tactile fever or palpable spleen. At the conclusion of the mission, 28 patients were prospectively tested with an antigen-capture assay for P. falciparum to determine the PPV of clinical diagnosis vs definitive laboratory testing. RESULTS: During the study period, 1215 of 4064 (30%) patients were diagnosed with malaria based on clinical presentation. On our final day, 28 consecutive patients with a clinical diagnosis of malaria were tested using an antigen-capture assay for P. falciparum. Of those, 25 tested positive-yielding a PPV of 89% (CI 0.78-1.01). CONCLUSION: In a remote field setting where malaria is endemic/epidemic, diagnosis of malaria based on selected historical and physical findings is possible with a high positive predictive value.